Influence of Vitamin D supplementation on reproductive outcomes of infertile patients: a systematic review and meta-analysis

Abstract

Background Low vitamin D status has been associated with an increased risk for infertility. Recent evidence regarding the efficacy of vitamin D supplementation in improving reproductive outcomes is inconsistent. Therefore, this systematic review was conducted to investigate whether vitamin D supplementation could improve the reproductive outcomes of infertile patients and evaluate how the parameters of vitamin D supplementation affected the clinical pregnancy rate. Methods We searched seven electronic databases (CNKI, Cqvip, Wanfang, PubMed, Medline, Embase, and Cochrane Library) up to March 2022. Randomized and cohort studies were collected to assess the reproductive outcomes difference between the intervention (vitamin D) vs. the control (placebo or none). Mantel-Haenszel random effects models were used. Effects were reported as odds ratio (OR) and their 95% confidence interval (CI). PROSPERO database registration number: CRD42022304018. Results Twelve eligible studies (n = 2352) were included: 9 randomized controlled trials (RCTs, n = 1677) and 3 cohort studies (n = 675). Pooled results indicated that infertile women treated with vitamin D had a significantly increased clinical pregnancy rate compared with the control group (OR: 1.70, 95% CI: 1.24–2.34; I2 = 63%, P = 0.001). However, the implantation, biochemical pregnancy, miscarriage, and multiple pregnancy rates had no significant difference (OR: 1.86, 95% CI: 1.00–3.47; I2 = 85%, P = 0.05; OR: 1.49; 0.98–2.26; I2 = 63%, P = 0.06; OR: 0.98, 95% CI: 0.63–1.53; I2 = 0%, P = 0.94 and OR: 3.64, 95% CI: 0.58–11.98; I2 = 68%, P = 0.21). The improvement of clinical pregnancy rate in the intervention group was influenced by the vitamin D level of patients, drug type, the total vitamin D dosage, the duration, administration frequency, and daily dosage of vitamin D supplementation. The infertile women (vitamin D level < 30 ng/mL) treated with the multicomponent drugs including vitamin D (10,000–50,000 IU or 50,000–500,000 IU), or got vitamin D 1000–10,000 IU daily, lasting for 30–60 days could achieve better pregnancy outcome. Conclusion To the best of our knowledge, this is the first meta-analysis systematically investigated that moderate daily dosing of vitamin D supplementation could improve the clinical pregnancy rate of infertile women and reported the effects of vitamin D supplementation parameters on pregnancy outcomes. A larger sample size and high-quality RCTs are necessary to optimize the parameters of vitamin D supplementation to help more infertile patients benefit from this therapy.

No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study

“…However, some studies did not find this association ( Subramanian et al , 2022 ). Moreover, clinical evidence from various RCTs indicated that vitamin D supplementation did not improve miscarriage rates as expected ( Tamblyn et al , 2022 ; Zhou et al , 2022 ; Meng et al , 2023 ). Although abundant exposure to ultraviolet radiation during the summer leads to a significant increase in serum vitamin D levels, research has not found any evidence suggesting improved clinical pregnancy rates, live birth rates, or reduced miscarriage rates in women undergoing oocyte retrieval and embryo transfer during the summer ( Carlsson Humla et al , 2022 ).…”

“…Although the results of this article and current clinical research did not support the prevention of miscarriage through vitamin D supplementation before and during pregnancy ( Tamblyn et al , 2022 ; Zhou et al , 2022 ; Meng et al , 2023 ), we still advocate for the supplementation of vitamin D in women preparing for pregnancy and in pregnant women with vitamin D insufficiency or deficiency in achieving normal levels of serum 25OHD. Pregnant women have an increased demand for vitamin D during pregnancy.…”

“…Furthermore, studies have indicated that vitamin D supplementation could reduce the occurrence of adverse maternal and fetal events such as preeclampsia, gestational diabetes mellitus, low birth weight, and preterm delivery ( Rostami et al , 2018 ; Tamblyn et al , 2022 ). Additionally, some studies have suggested potential benefits of vitamin D supplementation in enhancing clinical pregnancy rates for infertile women ( Meng et al , 2023 ).…”

Management strategies following implantation failure of euploid embryos

“…Although the European Society of Human Reproduction and Embryology (ESHRE) guideline for RIF does not recommend vitamin D testing and replacement given the lack of established evidence, 3 a recent systematic review and meta‐analysis demonstrated that clinical pregnancy rates in IVF treatment were increased by 2.06‐fold after vitamin D replacement in women with 25OHVD levels <30 ng/mL (95% CI: 1.32–3.22). 75 Among such women, those who received daily supplementation for >30 days had significantly better clinical pregnancy rates, compared to weekly or longer intervals and/or <30 days. In our previous report, vitamin D replacement at 25 μg/day for 3 months in patients with 25OHVD levels <30 ng/mL promoted sufficient levels in only half of them.…”

Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis

“…VDR null mice have also shown uterine hypoplasia and are responsive to estrogen priming, indicating the role of hypogonadism in uterine defects [ 91 ]. Based on a meta-analysis, a moderate daily intake of vitamin D supplements may enhance the chances of clinical pregnancy in infertile women and can have a positive impact on pregnancy outcomes [ 92 ].…”